The aim of this study is to better understand the central factors involved in the etiopathogenesis of altered pain perception in fibromyalgia (FM). We will test six hypotheses drawn from a model which posits that neuro- endocrine and immunologic abnormalities, characterized by decreases in cerebrospinal fluid (CSF) serotonin and increases in SCF substance P (SP), lead to sensitization of central nervous system structures involved in pain perception, i.e., thalamus and caudate nucleus. Decreases in regional cerebral blood flow (rCBBF) to these structures serve as markers for this sensitization process and are associated with generalized low pain thresholds and other alterations in pain perception, independently of the effects of psychiatric morbidity or psychological status. The model also posits that elevated CSF SP may in part be due to SP messenger (m) RNA production by CSF leukocytes. We propose to measure (1) rCBF to cortex, thalamus, and caudate nucleus, (20 CSF levels of serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), SP, CSF leukocyte number, and leukocyte SP mRNA level, (3) pain thresholds and indices of sensory discrimination ability and response bias in response to dolorimeter stimulation of tender and control points, and (4) psychological status and number of lifetime psychiatric diagnoses. These variables will be assessed using (1) 80 patients with FM by American College of Rheumatology (ACR) criteria drawn from the Rheumatology clinics at UAB and Cooper Green Hospital ("Patients"), (2) 50 cmmunity residents of comprable age, gender, education, and race with musculoskeletal pain who fulfill ACR criteria for FM, but who have not sought medical care for their symptoms in the past 10 years ("Non-Patients"), and (3) 50 community residents of comparable demographic features without musculoskeletal pain who do not fulfill ACR criteria for FM ("Controls"). The use of non-patients, who do not differ from controls in psychiatric morbidity, will allow us to determine if altered levels of rCBF to the thalamus and caudate nucleus are associated with pain perception and neurochemical levels regardless of subjects' psychiatric histories. This study is the first to examine relationships among rCBF to central structures and neurotransmitters involved in pain perception and subjects' responses to noxious stimuli while controlling for psychological variables. The results of this study will advance our knowledge regarding the roles of the central nervous system and neuroendocrine and immunologic abnormalities involved in altered pain perception among patients and community residents with FM. In addition, the results of the project may lead to development of pharmacologic interventions that will normalize rCBF to central brain structures and thus decrease pain among patients with FM.